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PubMedDate not supplied

Optimal temperature control policy for a two-stage recombinant fermentation process.

The optimal temperature control policy to be followed in the operation of a two-stage fermentation system in which gene expression is induced by a temperature-sensitive gene switching system was studied. A genetically structured model was used to describe product formation, and kinetic equations based on experimental data were used to quantify the specific gene expression rate and parameters that affect plasmid instability. A constant temperature control policy and temperature profiling control policy including temperature cycling were studied and compared. Maximum average production rate was obtained from a temperature control policy in which the second stage was operated initially at about 40.5 degrees C and the temperature decreased slightly to a constant value at 40.0 degrees C. The maximum average production rate, which corresponds to the optimal temperature control policy, for an operation of 180 h was 29.7 units of protein (mg of cells)-1 h-1.

DNA, Recombinant↗

PubMed1986

Effect of optimal glycaemic control with continuous subcutaneous insulin infusion on energy expenditure in type I diabetes mellitus.

To assess the role of insulin in the control of body weight energy expenditure was measured by indirect calorimetry in eight patients of normal weight with type I diabetes initially while poorly controlled during conventional insulin treatment and later during optimal glycaemic control achieved by using the continuous subcutaneous insulin infusion pump. Their response to seven days of fat supplementation was also assessed and the results compared with those in eight non-diabetic subjects. After a mean of 5.3 months of continuous subcutaneous insulin infusion the diabetic subjects had gained on average 3.5 kg. In the poorly controlled diabetic state the resting metabolic rate was raised but decreased by a mean of 374 kJ (90 kcal) per 24 hours with optimal glycaemic control. The thermic response to infused noradrenaline was reduced by 59% in the diabetic subjects, was not improved by continuous subcutaneous insulin infusion, but was improved when three of the subjects were given metformin in addition. The diabetic subjects had no abnormality in the thermic response to a meal while taking their usual diabetic diet. During fat supplementation, however, this thermic response was reduced when glycaemic control was poor but not when control was precise. Fat supplementation did not alter the resting metabolic rate or the reduced noradrenergic thermic response in the diabetic subjects. These findings suggest that precise glycaemic control could produce weight gain if energy intake remained unaltered, for diabetic subjects do not compensate for the decrease in metabolic rate by an increase in noradrenergic and dietary thermic responses. Also precise glycaemic control using continuous subcutaneous insulin infusion does not correct all the metabolic abnormalities of diabetes mellitus.

Adult↗

PubMedDate not supplied

Effect of transcription promoters on the optimal production of secreted protein in fed-batch reactors.

Production of heterologous proteins by yeast secretion imposes additional factors that need to be considered, which do not appear with production by direct expression. These include additional intracellular polypeptide processing dynamics through the secretory organelles and the protein concentration in the culture medium, which is the usual final destination of the product. Optimal control theory is applied to optimize fed-batch production of secreted protein. We maximize an objective function that includes both total production rate and product concentration. A mutant invertase is chosen as the model heterologous secretory protein. Optimal control control strategies have been obtained for the use of two different promoters for the gene transcription, a dere-pressible SUC2 promoter and a strong glycolytic GPD promoter. With the use of the strong GPD promoter, achieving maximum production occurs on the singular arc of maximum specific growth rate. As the object switches to maximum product concentration, operation occurs for longer periods of time at a slow glucose singular arc condition. The optimal control for maximizing protein production with the weak SUC2 promoter requires transitions between high and low glucose concentrations associated with multiple distinct singular arc conditions. For maximum product concentration, the high concentration branches of the singular arc supporting maximum growth rate and maximum secretion rate disappear. Operation stays essentially on the low glucose concentration branch of the singular arc, which maximizes the protein production rate and minimizes the dilution of the broth product concentration.

Cloning, Molecular↗

PubMed1992

Optimal chemical control of populations developing drug resistance.

A system of differential equations for the control of the growth of certain populations by the use of chemical treatment is presented. Rather general growth rates and kill rates of drugs, as well as drug resistance, are considered. A class of optimal control problems with a performance criterion depending on a parameter is formulated and shown to admit the same basic optimal strategy. Applications to cycle nonspecific chemotherapy and control of the growth of bacterial populations in cellulose media in paper production plants are described.

Antineoplastic Agents↗

PubMed1993

The relative importance of dispositional optimism and control appraisals in quality of life after coronary artery bypass surgery.

Similar mechanisms have been proposed to explain the stress-buffering effects of both dispositional optimism and perceived control. Yet dispositional optimism as a personal resource should function independently of situational control appraisals. To evaluate the unique and additive contributions to adaptation of control appraisals and optimism, we followed 49 individuals scheduled for coronary artery bypass surgery. One month before surgery dispositional optimism was associated with neither health locus of control nor specific expectancies about the outcomes of surgery. Dispositional optimism, however, was associated with perceived control over the course of the illness and with quality of life appraisals. Although presurgery optimism predicted life quality 8 months after surgery, this was not the case when general and specific control appraisals and specific expectancies were included in the prediction. These findings are discussed as they relate to current conceptions of trait optimism.

Adaptation, Psychological↗

PubMed1998

Optimizing gaze control in three dimensions.

Horizontal and vertical movements of the human eye bring new objects to the center of the visual field, but torsional movements rotate the visual world about its center. Ocular torsion stays near zero during head-fixed gaze shifts, and eye movements to visual targets are thought to be driven by purely horizontal and vertical commands. Here, analysis of eye-head gaze shifts revealed that gaze commands were three-dimensional, with a separate neural control system for torsion. Active torsion optimized gaze control as no two-dimensional system could have, stabilizing the retinal image as quickly as possible when it would otherwise have spun around the fixation point.

Adult↗

PubMed2006

Validation of serum versus plasma measurements of chromogranin a levels in patients with carcinoid tumors: lack of correlation between absolute chromogranin a levels and symptom frequency.

OBJECTIVE: Chromogranin A (CGA) levels are used to confirm the diagnosis and monitor the course of patients with neuroendocrine tumors. Chromogranin A levels are significantly reduced when patients are acutely treated with octreotide; however, limited data are available that correlates octreotide long-acting repeatable (LAR) dose or steady state octreotide blood levels to the absolute value of serum or plasma CGA. METHODS: Plasma, serum, and clinical information on carcinoid syndrome symptoms were collected anonymously from 40 patients treated with long-term octreotide LAR therapy for carcinoid syndrome. RESULTS: We found a strong positive linear relationship exists between serum and plasma CGA levels (r = 0.9858, P < 0.0001). No correlation existed between plasma octreotide levels or LAR dose and the static, absolute plasma/serum CGA levels. Although, higher mean CGA values were seen in the group whose diarrhea was "not under optimal control" than for the group "under optimal control," these results did not reach statistical significance (P = 0.24). Contrary to our hypotheses, a statistically significant inverse relationship was found between the frequency of flushing and the CGA levels (P = 0.0372). Higher mean CGA values were observed in the "under optimal control" group with flushing symptoms. CONCLUSIONS: Either serum or plasma can be used to measure CGA levels. Absolute (static) CGA levels do not positively correlate with symptom intensity during LAR therapy. Dynamic (serial) measurements of CGA are necessary to monitor the effectiveness of medical or surgical therapy.

Antineoplastic Agents, Hormonal↗

PubMed1989

Oral controlled release optimization of pellets prepared by extrusion-spheronization processing.

Controlled release high dosage forms of a typical drug such as Indobufen were prepared as multiple-unit doses by employing extrusion-spheronization processing and subsequently film coating operations. The effects of drug particle size, drug/binder ratio, extruder screen size and preparation reproducibility on the physical properties of the spherical granules were evaluated. Controlled release optimization was obtained on the same granules by coating with polymeric membranes of different thickness consisting of water-soluble and insoluble substances. Film coating was applied from an organic solution using pan coating technique. The drug diffusion is allowed by dissolution of part of the membrane leaving small channels of the polymer coat. Further preparations were conducted to evaluate coatings applied from aqueous dispersion (pseudolatex) using air suspension coating technique. In this system the drug diffusion is governed by the intrinsic pore network of the membrane. The most promising preparations having the desired in vitro release, were metered into hard capsules to obtain the drug unit dosage. Accelerated stability tests were carried out to assess the influence of time and the other storage parameters on the drug release profile.

Cellulose↗

PubMed2004

Low order robust controller design for preserving Hinfinity performance: genetic algorithm approach.

This paper investigates the design of low order robust controllers based on an Hinfinity performance index using a real-code genetic algorithm. In Hinfinity controller design, the major disadvantage of the existing methods is that they lead to high-order controllers. This is the gap between theory and practice. Therefore the purpose of this paper is to design a low order controller with similar performance to the Hinfinity optimal controllers, which can find sufficiently wide use in engineering practice. We first design the Hinfinity optimal controller using Glover and Doyle's results, and obtain the corresponding performance index gamma. Second, the desired low order controller with several parameters is chosen, e.g., a first-order controller, or a PID controller. Finally, we use the real-code genetic algorithm to find the optimal controller parameters that preserve the performance index y. Computational simulations illustrate the effectiveness of the proposed approach.

Journal Article↗

PubMed2004

Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial.

In preterm infants receiving supplemental oxygen, manual control of the inspired oxygen fraction is often time-consuming and inappropriate. We developed a system for automatic oxygen control and hypothesized that this system is more effective than routine manual oxygen control in maintaining target arterial oxygen saturation levels. We performed a randomized controlled crossover clinical trial in 12 preterm infants receiving nasal continuous positive airway pressure and supplemental oxygen. Periods with automatic and routine manual oxygen control were compared with periods of optimal control by a fully dedicated person. The median (range) percentage of time with arterial oxygen saturation levels within target range (87-96%) was 81.7% (39.0-99.8) for routine manual oxygen control, 91.0% (41.4-99.3) for optimal control, and 90.5% (59.0-99.4) for automatic control (ANOVA: p = 0.01). Pairwise post hoc comparisons revealed a statistically significant difference between automatic and routine manual oxygen control (Dunnett's test: p = 0.02). The frequency of manual oxygen adjustments was lowest in automatic control (Friedman's test: p < 0.001). Automatic oxygen control may optimize oxygen administration to preterm infants receiving nasal continuous positive airway pressure and reduce nursing time spent with oxygen control.

Automation↗

PubMed2006

[Comparison of a propofol-based anesthesia regimen using optimated-target-controlled-infusion (OTCI) and manually-controlled infusion (MCI) technique].

BACKGROUND: Propofol anesthesia based on target-controlled-infusion (TCI) has been shown to be superior to a manually-controlled-infusion (MCI) technique. A new optimal-target-controlled-infusion (OTCI) technique enables an individual plasma-targeted adjustment by including the concentration in the effect-compartment. This study compared practicability and costs of the new system with a conventional MCI-based propofol anesthesia regimen. METHODS: In a prospective study, 50 patients scheduled for elective surgery of nose or nasal sinuses were randomly enrolled to receive BIS-controlled anaesthesia (level: 40-55) using either OTCI (n = 25) or MCI (n = 25). Hemodynamics, extubation times and time of awaking, rate and quality of propofol adjustment, total drug requirements, costs, postanaesthetic care unit (PACU) stay, Aldrete and pain scores, and adverse effects (postoperative nausea and vomiting (PONV), shivering) were recorded. RESULTS: Demographics, hemodynamics, and perioperative data including extubation times were comparable for both study groups. Propofol consumption was similar within the first 60 min for both groups, thereafter, significantly less propofol in the OTCI group (5.03 mg/kg/h) than the MCI group (5.79 mg/kg/h) was used. Costs for propofol was significantly reduced with OTCI (0.2 vs. 0.23 Cent/anaesthesia minute/kg), the administration of other anaesthetics (fentanyl, remifentanil, cis-atracurium) did not differ between the groups. The number of infusion adjustments to BIS values were not significantly different. CONCLUSION: The new OTCI-system is a safe and easily controllable technique. The obvious advantage of this infusion system appears to be a reduction in propofol consumption and direct drug costs for anaesthesia lasting longer than 60 min.

Adolescent↗

PubMed2004

Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention.

OBJECTIVES: We examined the association between glycemic control determined by preprocedural hemoglobin A1c (A1c) and the incidence of target vessel revascularization (TVR) in diabetic patients undergoing elective percutaneous coronary intervention (PCI). BACKGROUND: Patients with diabetes mellitus (DM) have increased rates of restenosis and a worse clinical outcome after PCI than patients without DM. METHODS: A total of 239 patients (60 without DM and 179 with DM) were enrolled in this study. Optimal glycemic control was defined as A1c < or =7%, and suboptimal control was defined as A1c >7%. Follow-up was performed at six and 12 months after the index intervention. RESULTS: Diabetic patients with optimal glycemic control had a rate of 12-month TVR similar to that of nondiabetic patients (15% vs. 18%, p = NS). Diabetic patients with A1c >7% had a significantly higher rate of TVR than those with A1c <7% (34% vs. 15%, p = 0.02). In a multiple logistic regression analysis, A1c >7% was a significant independent predictor of TVR (odds ratio 2.87, 95% confidence interval 1.13 to 7.24; p = 0.03). Optimal glycemic control was associated with a lower rate of cardiac rehospitalization (15% vs. 31%, p = 0.03) and recurrent angina (13% vs. 37%, p = 0.002) at 12-month follow-up. CONCLUSIONS: In diabetic patients undergoing elective PCI, optimal glycemic control (A1c < or =7%) is associated with a lower rate of TVR, cardiac rehospitalization, and recurrent angina. These data suggest that aggressive treatment of DM to achieve A1c < or =7% is beneficial in improving the clinical outcome after PCI.

Aged↗

PubMed1994

Optimal adaptive control of pharmacodynamic effects with aminoglycoside antibiotics: a required approach for the future.

Many factors are considered in designing optimal drug regimens, including dose, route of administration, and the frequency and rate of administration. It is evident that the first parameter to be considered in dosage regimen determinations is the pharmacokinetics of the drug in the treated patient, or more extensively in the corresponding specific population of patients characterized by a similar pathophysiological status, e.g. neutropenics, ICU patients, subjects with renal insufficiency, children, geriatrics... Therefore, over the last two decades, pharmacokinetic principles have widely, and almost exclusively influenced the optimal adaptative control of antibiotics with a small therapeutic index. The large number of available new drugs associated with medical progress, specially in considering the increase of surviving patients with severe diseases or precarious physiopathological status (e.g., neutropenia, AIDS, ICU patients ...) have demonstrated the limits of this approach and pointed out the necessity of the determination of suitable parameters reflecting the in vivo efficacy. Thus, the search for pharmacodynamic parameters that can be accurately related to pharmacokinetic profiles in patients becomes a major tool. The progress in measurement of antibiotics and the additional dimension of the antibiotic's efficacy evaluation based on the analysis of the time course of the antibacterial effects, have provided the basis for the coupled evaluation of pharmacokinetics and pharmacodynamics of antibiotics, which has been largely assessed by in vivo animal models. In an attempt to propose a methodology that can provide information directly applicable to patients to be treated, we have developed a human in vivo/ex vivo model of analysis of the pharmacodynamics of antibiotics. This model has been applied to several drugs and particularly to aminoglycosides. It allows one to have a more rational evaluation of the dose-concentration-effect relations for antibiotics in man. The pharmacodynamics of aminoglycosides is characterized by a strong concentration dependent bactericidal activity and a significant post-antibiotic effect against Gram-negative bacilli. Experimental animal studies confirmed by investigations in man have shown that in vivo efficacy is enhanced by increasing the Cmax and the AUC of these antibiotics regardless of the possible below-MIC value of the C min. Moreover, the in vivo efficacy seems to be the same whether the total dose of aminoglycoside is given as a once a day dosing or as several doses while the toxic risk appears to be attenuated by the first dosage schedule. These data also emphasize the need for the development of models and software for optimal adaptive control including the pharmacodynamic parameters of antibiotics.

Aged↗

PubMed1999

Patient-controlled analgesia: optimizing the experience.

A patient-controlled analgesia (PCA) program was established on a surgical unit with children age 7 years and older. The primary objectives for the PCA program were safety and efficacy. A retrospective evaluation of the first 30 patients enrolled in the program suggested in the program suggested that it was safe and adequately controlled pain for all but 4 patients. A chart review of these patients indicated that the relation between the number of failed administration attempts, the total hourly analgesic intake, and the pain intensity score was key to optimizing the use of PCA. Recommendations to strengthen the PCA program were implemented based on information gained from these 4 patients with poorly controlled pain.

Adolescent↗

PubMed2000

Optimal asthma control, starting with high doses of inhaled budesonide.

The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks (double-blind), then 1,600 microg x day(-1) for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1-16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose. By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200- and 1,600-microg x day(-1) starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L x min(-1), p=0.8). Subjects starting with 3,200 microg x day(-1) were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of > or = 3.92 micromol by week 16 (p=0.03) [corrected]. During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 microg x day(-1), p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days x week(-1), beta2-agonist use 0.2 occasions x day(-1), and PD20 2.4 micromol). In subjects with poorly controlled asthma, a starting dose of 1,600 microg x day(-1) budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation.

Administration, Inhalation↗

PubMed1997

The economic aspects of drug delivery in asthma.

The need for cost-effective asthma therapy is driven by the high prevalence of asthma as well as the high cost of both medical care and lost productivity through illness. Limited healthcare resources demand proven therapies that maintain sustained disease control. Optimal disease control is the essence of cost effectiveness, but this in turn is dependent on correct drug selection and appropriate drug delivery. Successful treatment depends on delivery of medication to the site of action in the airways. Although there is a substantial number of aerosol delivery systems available, there is considerable confusion as to the most suitable method in different clinical settings, and across different age groups. Optimal drug delivery can be achieved without adding substantially to the overall cost of therapy. Both drugs and delivery systems need to be individualised to the needs of the patients. The early introduction of oral corticosteroids for acute exacerbations has resulted in reduced hospitalisation and shortened illness, providing substantial cost savings. A reduction in the reliance on nebuliser therapy in both the acute and chronic setting will further optimise therapy and reduce costs. We have reviewed the current literature to determine the most cost-effective methods of drug delivery in asthma.

Asthma↗

PubMed1999

An evaluation of oxidative stress in diabetes mellitus during uncontrolled and controlled state and after vitamin E supplementation.

OBJECTIVE: The study was conducted on 50 patients (10 insulin dependent diabetes mellitus (IDDM) and 40 non-insulin dependent diabetes mellitus (NIDDM) of recently diagnosed diabetes mellitus. The main objectives of the study were: 1. To evaluate oxidative stress at uncontrolled stage. 2. To evaluate the effect of optimal control on oxidative stress irrespective of type of drug therapy used. 3. To further evaluate the effect of vitamin E supplementation on oxidative stress after achieving optimal control. This was done in order to explore anti-oxidant effect of vitamin E. METHODS: Fifty patients of uncontrolled diabetes of less than 1 year duration and without any overt complications were studied. The parameters of oxidative stress included malonyl-di-aldehyde (MDA), reduced glutathione and vitamin E levels in the blood. They were done at three stages i.e. (a) In uncontrolled stage, (b) At controlled stage and (c) After 4 weeks of vitamin E supplementation in dosage of 400 mg daily. The parameters of control included fasting blood sugar < or = 140 mg%, post prandial < or = 200 mg and HbA1c < or = 7% (analysed by prepared kit). RESULTS: The significantly raised levels of MDA and decreased levels of reduced glutathione and vitamin E during uncontrolled stage of diabetes indicated free radical stress inducing lipid peroxidation. The significant fall of MDA and rise in reduced glutathione and vitamin E levels in blood after optimal control revealed its beneficial effect on oxidative stress. The levels were not normalised but still stayed higher than controls. After 4 weeks of vitamin E supplementation, further fall in MDA and rise in reduced glutathione suggested beneficial effect of vitamin E over and above the optimal control. Vitamin E estimation in blood at this stage did not constitute parameter of oxidative stress as it was provided from outside but was done to know the compliance of patients. Normalisation or near normalisation was not achieved with vitamin E therapy indicating persistence of oxidative stress. CONCLUSION: There was an evidence of oxidative stress in diabetes which decreased with optimal control and further declined after vitamin E supplementation indicating anti-oxidant effect of vitamin E alone. Normalisation of oxidative stress was not achieved. A further study is desired to study the effect of vitamin E for longer period at least 3-6 months before a definite conclusion is drawn.

Adult↗

PubMed2002

Influenza in the acute hospital setting.

Influenza poses special hazards inside healthcare facilities and can cause explosive outbreaks of illness. Healthcare workers are at risk of acquiring influenza and thus serve as an important reservoir for patients under their care. Annual influenza immunisation of high-risk persons and their contacts, including healthcare workers, is the primary means of preventing nosocomial influenza. Despite influenza vaccine effectiveness, it is substantially underused by healthcare providers. Influenza can be diagnosed by culturing the virus from respiratory secretions and by rapid antigen detection kits; recognition of a nosocomial outbreak is important in order to employ infection-control efforts. Optimal control of influenza in the acute-care setting should focus upon reducing potential influenza reservoirs in the hospital, including: isolating patients with suspected or documented influenza, sending home healthcare providers or staff who exhibit typical symptoms of influenza, and discouraging persons with febrile respiratory illness from visiting the hospital during a known influenza outbreak in the community. (Note: influenza and other respiratory viruses can cause non-febrile illness but are still transmissible.) The antiviral M2 protein inhibitors (amantadine, rimantadine) and neuraminidase inhibitors (zanamivir, oseltamivir) have proven efficacy in treating and preventing influenza illness; however, their role in the prevention and control of influenza in the acute hospital setting remains to be more fully studied.

Acetamides↗